Michigan Alzheimer's Disease Research Center (MADRC) [unreadable] In this competing continuation application, we propose to initiate three new scientific projects, continue an active pilot grants program, and support multiple scientific investigations of the dementias funded through additional NIH grants utilizing four cores, Administrative, Clinical, Data Management and Statistics and Neuropathology. All three new projects investigate Alzheimer's disease (AD), and two focus on the transition from normal aging to mild cognitive impairment (MCI) and subsequent dementia. Project 1 will examine the mechanism underlying the inhibitory effects of X11a upon cleavage of amyloid precursor protein utilizing transgenic and knockout mice and probe the genetic linkage of X11a to chromosome 9. Project 2 will determine whether positron emission tomography (PET) with [unreadable] fluorodeoxyglucose can predict the rate of progression of dementia in MCI and mild dementia. Project 3 will evaluate the risk factors, clinical characteristics and outcomes of cognitive impairment that does not meet criteria for dementia (CIND) and its subtypes. A minority satellite diagnostic and treatment center will continue to recruit underrepresented urban, predominantly African American, patients to research studies. The scientific approaches utilize major strengths in neurology, neuroscience and epidemiology at the University of Michigan, including the availability of large numbers of normal aged subjects, patients with MCI and with AD, longitudinal studies with autopsy verification, biostatistics, [unreadable] PET, molecular biology, molecular pharmacology, and survey research. The MADRC interacts with multiple components of the University to achieve its scientific and educational objectives, particularly the Schools of Medicine, Public Health, and Nursing; the Institute for Social Research; Claude Pepper Center, Nathan Shock Center, Institute of Gerontology, and Geriatric Research Education and Clinical Center at the Ann Arbor Veterans Affairs Medical Center, It collaborates with other ADCs on research projects and with the National Alzheimer's Coordinating Center in datasharing. It plays a leadership role in statewide dementia initiatives and works closely with national and local chapters of the Alzheimer Association. It provides a rich environment for attracting fellows, junior and senior scientists into cutting-edge basic and clinical research. [unreadable] [unreadable]